Fetal fibronectin in cervicovaginal secretions as a predictor of preterm birth

Abstract

Objective To determine whether fetal fibronectin detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labour is a predictor for preterm birth. Design A blind prospective observational study. Setting A teaching hospital. Participants One hundred and forty‐one women presenting to the delivery suite between 24 and 37 weeks of gestation (112 were between 24 and 34 weeks of gestation) with symptoms suggestive of preterm labour, with intact membranes and cervical dilatation of < 2 cm. Intervention Specimens of cervicovaginal secretions were collected from the ectocervix and posterior fornix. Fetal fibronectin levels were measured by an ELISA and samples were considered positive if the level of fetal fibronectin present was ≥ 0.05 μg/ml. Main outcome measures Gestation at birth and sampling‐birth interval. Results The preterm birth (before 3 7 weeks of gestation) rate in the population studied was 19±1%. Fetal fibronectin predicted preterm birth with sensitivity of 63%, specificity of 95±6%, positive predictive value of 77±3%, and negative predictive value of 91±6%. Analysis of the data from women at less than 34 weeks of gestation showed similar results. A negative test accurately excluded (97±9%) the chance of subsequent birth during the three weeks interval following sampling. Conclusions The presence of fetal fibronectin in the cervicovaginal secretions of women admitted with symptoms suggestive of preterm labour indicates a significant risk for subsequent preterm birth. The absence of fetal fibronectin in this group is a very strong indication that subsequent preterm birth is unlikely to occur. Fetal fibronectin test, if combined with clinical findings, has a potentially important role in clinical management of women with symptoms suggestive of preterm labour.

Prediction of spontaneous preterm labour in at-risk pregnant women

“…The efficacy of these commercially available tests relies on the abnormal presence of either fetal fibronectin (fFN) or phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP1) in the cervicovaginal fluid (CVF). The detection of these proteins in the CVF indicates a disruption at the choriodecidual interface that in turn could lead to subsequent (preterm) birth (Malak et al 1996, Elizur et al 2005. The fFN test in particular has limited utility to predict PTL due to its low positive predictive value (PPV) as well as false-positive results caused by recent unprotected sexual intercourse.…”

Accuracy of cervico-vaginal fetal fibronectin test in predicting the risk of spontaneous preterm birth—a systematic review

“…If we treated only those women with a positive test result we would need to treat 17, a figure considerably lower than that without testing This approach will allow clinicians to make explicit decisions on the basis of more realistic probabilities generated by fibronectin testing and provides a framework for the use of diagnostic evidence in therapeutic decision making. Specifically, our results enable clinicians to make a more rational approach to Peaceman (1997) 65 Lukes (1997) 62 Peaceman (1996) 65 Iams (1995) 60 Giles (2000) 58 Benattar (1997) 22 Lopez (2000) 59 Malak (1996) 63 Coleman (2001) 47 McKenna (1999) 64 McKenna (1999) 64 Senden (1996) 50 LaShay (2000) 51 Bartnicki (1996) 21 Leeson (1996) 61 Peaceman (1997) 65 Coleman (1998) 46 Overall (95% CI) Likelihood ratios for positive test result…”

“…Future research should focus on undertaking high quality primary studies of test accuracy to improve our ability to predict spontaneous preterm birth. Peaceman (1997) 65 Peaceman (1997) 65 Lockwood (1991) 8 Rizzo (1997) 92 Rizzo (1996) 91 Rizzo (1996) 91 Bartnicki (1996) 21 Iams (1995) 60 Malagrida (1995) 82 Calda (1995) 85 Lopez (2000) 59 Malak (1996) 63 Irion (1995) 88 Rozenberg (1997) 93 Hampl (1994) 54 Mansouri (1997) 98 Chuileannain (1998) 95 Giles (2000) 58 Malagrida (1995) 82 Langer (1997) 89 Goffeng (1997) LaShay (2000) 31 Benattar (1997) Inglis (1994) 79 Peaceman (1997) 65 Vetr (1996) 96 Grandi (1996) 48 Surbek (1997) 83 Roubille (1999) 84 Vercoustre (1996) 81 Vercoustre (1996) 81 Nageotte (1992) 70 Morrison (1993) 49 Overall (95% CI) …”

Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition

“…The tissue remodelling associated with the zone of altered morphology almost certainly is a consequence of the secretion and activation of matrix metalloproteinase (MMP) enzymes, which act to break down the supporting extracellular matrix. In human and rat fetal membranes, an increase in MMP-9 activity has been demonstrated at the time of labour (Vadillo-Ortega et al 1990, Riley et al 1996, and extracellular matrix proteins in the fetal membranes, such as oncofetal fibronectin, can be detected in cervical mucus with the onset of labour (Malak et al 1996, Goldenberg et al 1997. MMPs may also contribute to labour by activating cytokines such as tumour necrosis factor (TNF ) (McGeehan et al 1994), releasing stimulatory signals bound to the extracellular matrix (Lala & Hamilton 1996) and by changing cellular signalling through uncoupling from matrix (Cross et al 1994, Damsky et al 1994.…”